This research project is undertaken to investigate chemical composition of subcellular organelles in epidermal cells at different stages of differentia- tion, and to examine chemical and morphological changes which occur in those organelles under experimental and pathological conditions. Light and electron microscopic autoradiography are used to determine specific chemical markers forn each organelle, and to examine synthesis and turnover of the marker consti- tuents. The radioactively marked constituents of organelles are then chemically isolated, in order to characterize the organedle components. Changes in chemical composition of the organelles in undifferentiated and differentiated ceells are compared. Chemically purified organelle constituents are used to raise antibodies in rabbits, and ultrastructural immunohistochemical techniques are applied to determine whether the chemical and immunological characteristics of these organelles alter in epidermal cells with abnormal keratinization under experimental and pathological conditions. Disease such as psoriasis, ichthyosis, verrucae and skin cancers are examined and specific chemical changes in each disease are sought. Chemical and ultrastructural changes which resemble those of the disease are produced in animals by administration of chemical and biological compounds, the activities of which are well established in cells other than epidermal. These animal models explain control mechanisms directly involved in these diseases.